One of the main objectives of the work carried out under NIH Grant AM11448 has been to investigate the genetic mechanism of x-ray induced lethal mutations at the albino locus of the mouse resulting in multiple enzyme deficiencies and in ultrastructural defects of the endoplasmic reticulum. The 3 enzymes which were found to be deficient in 4 different mutant strains were glucose-6-phosphatase, tyrosine aminotransferase, and serine dehydratase. Although these enzymes occur in different compartments of the cell, they have in common a rapid perinatal development. These and other findings (e.g., the absence of a gene dosage effect in the heterozygotes) were difficult to reconcile with the idea that the mutations were due to alterations in the structural genes for the respective enzymes. As a working hypothesis, the mutations are ascribed to an alteration of a regulatory gene which controls the appearance of these enzymes at birth. A new albino mutation, c6H, an early embryonal lethal in intraline crosses, has been found to produce viable albino offspring in interline crosses with any of the 4 previously investigated mutant strains (c14CoS, c3H, c65K and c112K) and to cause a return of enzyme levels to normal. A more detailed study of these crosses has led to the construction of a complementation. New work in progress involves (1) the so-called Cattanach translocation in which part of chromosome 7, including the albino locus, becomes attached to the X-chromosome. Cattanach females are crossed with heterozygous males of our mutant strains, producing a number of mosaic mice which will be analyzed for enzyme levels. (2) Fusion of mutant mouse liver cells with rat hepatoma cells, combined with methods to identify mouse and rat enzymes in the mouse-rat heterokaryon. (3) Isolation of mRNA from mutant and normal livers and study of these in a cell-free protein-synthesizing system.